Trump stirs autism storm, FDA backs leucovorin for kids, most docs (but not all) express outrage online
Industry Buzz
The data on leucovorin isn’t very strong... it can be mildly beneficial in some patients with autism. It’s not going to cure it. It’s just going to cause a massive headache for rheumatologists since they actually need to prescribe [it] to people with RA on methotrexate who can’t tolerate folic acid.
—Family medicine physician @wanna_be_doc
I’ve started [leucovorin] on a few autistic kiddos in my office. I give the parents the studies, talk about limited outcomes, but don’t see much downside in trying. So far I’ve seen some improvement in speech in these kids.
—Pediatrician @efox02
On the same day President Trump stirred controversy by linking autism risk to acetaminophen use during pregnancy, the FDA announced it would approve a new use for leucovorin, or folinic acid, to treat children with cerebral folate deficiency, an ultra-rare disorder that can present with autism-like features.[][][]
What caught physicians’ attention most, however, was the rhetoric during the September 22 press conference—and in an accompanying press release—in which senior administration health officials suggested that leucovorin could be offered to a much broader group of children with autism.[][]
What doctors are saying
In a post on r/medicine, a Reddit thread made up of physicians and other health experts, doctors expressed alarm about the recent announcements.
On the acetaminophen announcement, user @Sock_puppet09, an RN, brought up a salient point: "Wow, they’re even encouraging to not take [Tylenol] for fever, which has known teratogenic effects. How much disability is this going to cause?”
On the leucovorin announcement, @drhoudinimd, a rheumatologist, wrote, "Weren't these the same people who were demanding ‘placebo controlled trials’ for vaccines not too long ago? This isn't even [based on] a scientific study, it's just a poorly done meta analysis that was most likely designed to attract attention for Harvard and the authors but adds little to any scientific inquiry.”
User @wanna_be_doc, a family medicine physician, added, "The data on leucovorin isn’t very strong... At best it can be mildly beneficial in some patients with autism. It’s not going to cure it.It’s just going to cause a massive headache for rheumatologists since they actually need to prescribe leucovorin to people with RA on methotrexate who can’t tolerate folic acid."
It wasn’t all outrage, however. User @efox02, a pediatrician, wrote, “I’ve started [leucovorin] on a few autistic kiddos in my office. I give the parents the studies, talk about limited outcomes, but don’t see much downside in trying. So far I’ve seen some improvement in speech in these kids.”
User @NickDerpkins, an infectious disease expert (PhD), noted what some may consider a silver lining: “Best case scenario: multiple people with CFD have been misdiagnosed with ASD and will accidentally receive the right treatment.”
Leucovorin has a place in medicine, but is it here?
Leucovorin—the reduced form of folate, or folinic acid—has well-established roles in oncology and hematology; it’s used to counteract cancer drugs like methotrexate, to enhance other chemo drugs, and to treat some forms of anemia.[]
In autism spectrum disorder (ASD), research has highlighted two potential mechanisms: genetic variants that affect the body’s ability to process folate or autoimmune disorders that prevent the transport of folate to the brain. Cerebral folate deficiency has been associated with developmental delays and autism-like phenotypes.
What the science says
Several small randomized controlled trials have tested leucovorin in children with ASD, with mixed but intriguing findings. Some studies reported improvements in verbal communication, irritability, and adaptive behavior. Yet across trials, “the evidence … supporting [treatment with leucovorin] is really, really weak,” David Mandell, a professor of psychiatry and an autism expert at the University of Pennsylvania, told Reuters.[]
Methodological issues limit generalizability, and most experts caution against extrapolating results to the broader ASD population. Improvements in subgroups with documented folate transport dysfunction appear more reproducible, supporting the view that leucovorin may be a targeted therapy rather than a universal one.
The American Psychiatric Association released a statement soon after the announcement, reminding docs—and patients—to trust the literature: “It will require many more years of research before we know if leucovorin is an appropriate treatment for individuals with autism.”[]
The FDA’s move is unusual: The agency is re-establishing an NDA for a drug voluntarily withdrawn more than 20 years ago and broadening its scope from rare deficiency syndromes to potentially millions of children with autism. Critics argue that such a step, absent large, definitive phase 3 data, risks fueling off-label use without a sufficient evidence base. Others see it as an opportunity to spur more rigorous investigation of folate biology in neurodevelopmental disorders.
Related: Docs cheer after West Coast breaks from CDC with its own vaccine playbook: 'I can't tell you the relief I felt'What clinicians should keep in mind
For now, leucovorin may reasonably be considered only in ASD patients with confirmed cerebral folate deficiency or folate receptor autoantibodies, ideally within a research or specialty care context.
Extension of its use to the general autism population is not evidence-based at present, regardless of what senior health officials assert. Physicians should counsel families carefully, underscoring the difference between targeted therapy in well-defined subgroups vs broad, unproven application.
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